The present grant application is made for renewal of our GM26879 grant titled "Total Synthesis of Leuconolide A3" which expires August 31, 1982. Having successfully completed the synthesis of leucomycin A3 and carbomycin B we now propose to expand our program in the macrolide antibiotics area to include carbomycin A, protylonolide and tylosin. Our long-term plans also include initiation of work into a synthesis of the polyene macrolides such as the 36-membered ring macrolide amphotericin. Our main objectives in thenext three to four years are to explore and develop methodology for the utilization of Alpha-D-glucose as starting material for the total synthesis of the above mentioned macrolide antibiotics via convergent routes. The proposed methodology features (a) building both the left side (C10-C15 segment) and the right side (C1-C9 segment) from two molecules of Alpha- D-glucose in a stereocontrolled manner, (b) a ketophosphonate cyclization to build the macrocycle in a geometrically selective way and (c) stereoselective glycoside bond formation for the attachmednt of the carbohydrate units for the completion of the tylosin synthesis. It is expected that new synthetic methodology in the areas of carbohydrate utilization in the synthesis of complex molecules and glycoside bond formation will emerge from this program. Furthermore, the expected syntheses will allow the production of a number of novel analogs of these important antibiotics, otherwise unavailable for biological evaluation.